Recreational use of prescription opioids among adolescents is a significant and growing public health concern and has been referred to as an emerging epidemic in the U.S. Although a number of science-based, interactive, drug-abuse prevention programs exist focused on preventing use of non-prescription drugs among youth, to our knowledge, no science-based, interactive program focused on the prevention of prescription opioid abuse among youth exists. Given that adolescents' views about the recreational use of prescription opioids differ in systematic ways from use of illegal, non-prescription drugs, developing an effective prevention program for youth targeted specifically at prescription opioid abuse is critical. In this project, we propose to develop an interactive, computer program focused on the prevention of prescription opioid abuse among high school-aged adolescents. This program will be grounded in a scientific understanding of risk factors for prescription opioid abuse among youth, employ informational technologies which are effective in promoting relevant knowledge and skills, and present program content using strategies which have been shown to be highly appealing to adolescents. In Phase I of this project, we developed and demonstrated the scientific, technical and commercial merit and feasibility of a prototype of a web-based, prescription opioid abuse prevention program for high school-aged youth. Phase I results clearly demonstrated the acceptability and potential utility of the prototype of this program to the target audience. Participants' rated the program very positively, and their knowledge related to prescription opioid abuse prevention markedly increased from low baseline levels to perfect or near perfect levels after completing the program prototype. In this Phase II application, we plan to complete the development of all components of the multimedia, prescription opioid abuse prevention program and conduct a randomized, controlled trial with high school-aged youth (ages 14-18 years) to evaluate the effectiveness of the web-based prevention intervention in increasing knowledge about key issues relevant to prescription opioid abuse among youth, skills acquisition relevant to preventing their misuse, negative attitudes about prescription opioid misuse, and perceived risk associated with their misuse. We will also assess the intervention's effectiveness in reducing intentions to misuse prescription opioids as well as actual rates of such use. The proposed computer program will be developed as a browser-based program which can be delivered via Internet, intranet or via CD-ROM installation, which allows for its use in a wide variety of settings (e.g., online, home, school, community organizations, health care providers offices). This program may provide an innovative, engaging, effective and potentially cost-effective tool for promoting the widespread delivery of science-based prevention of prescription opioid abuse among adolescents.